Acute Lung InjuryNCT03317431
the Effect of Dopamine on Mechanical Ventilation Induced Lung Injury
An observational study of Acute Lung Injury, run by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial summary
Dopamine(DA) is a common neurotransmitter that has been known to regulate behavior, movement, cardiovascular，endocrine and gastrointestinal functions, but also functions as an important molecule engaging in the immune systems to possess anti-inflammatory effects. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Acute Lung Injury
- What is being tested?
- mechanical ventilation
- How many people
- 46 participants
- Where
- 1 siteChina
- Study dates
- 20 Mar 2017to 1 Dec 2017
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Study population: patients undergo elective lobectom
Who may be able to join
- Patients inclusion criteria: undergo elective lobectomy with general anesthesia and mechanical ventilation; classified as physical status I to III according to the American Society of Anesthesiologists Physical Status Classification System; Written informed consent is approved.
Who cannot join
- Distant metastases: recent anaesthetics or mechanical ventilation treatment；children；women during pregnancy or lactation; being involved in other clinical subjects.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Anesthesia, Shanghai Xinhua hospital
Shanghai, Shanghai Municipality, 200082
About this study
Official title: the Mechanism of the Downregulation of Dopamine Receptor in Mechanical Ventilation Induced Lung Injury
Dopamine(DA) is a common neurotransmitter that has been known to regulate behavior, movement, cardiovascular，endocrine and gastrointestinal functions, but also functions as an important molecule engaging in the immune systems to possess anti-inflammatory effects. However, its role in ventilator-induced lung injury (VILI) is still unclear. Herein, this study aimed to investigate the therapeutic efficacy of dopamine on ventilation-induced lung endothelial barrier dysfunction and explore the possible underlying molecular mechanisms.
Read the detailed description
Mechanical ventilation is a critical intervention for patients with acute respiratory failure. However, lung overdistension induced by mechanical ventilation at high tidal volumes also causes pulmonary endothelial dysfunction. The injurious effect of mechanical stretch on pulmonary endothelium has been implicated in the development of ventilator-induced lung injury (VILI), which is characterized by pulmonary inflammation and particularly increased vascular permeability. In addition, the investigators and others have previously shown that mechanical stretch increases cultured lung endothelial monolayer permeability in vitro and promotes lung vascular permeability in mice Thus, elucidating the mechanisms underlying the mechanical stretch-induced lung endothelial barrier dysfunction may provide a novel clinical therapeutic target against VILI.
Dopamine is a neurotransmitter, which can also be produced outside the central nervous system. Lung alveolar epithelial cells represent an important source of extraneuronal dopamine, which has a significant role in local organ physiology. Dopamine D1 receptor (DRD1) and D2 receptor (DRD2) are present in lung tissues. Activation of D2DR induces NaKATPase gene expression. Moreover, activation of DRD1 results in the trafficking of NaKATPase to the basolateral membrane of type II alveolar epithelial cells, thus increasing lung liquid clearance during acute lung injury. Although the lung-protective effects of DA and its implication in the pathology of ALI are emerging, the mechanisms are still largely unknown.
In the present study, the investigators will analyze the influence of mechanical ventilation on dopamine receptors in the lung tissue of the participants, and explore whether DA could protect ventilation induced lung injury, which is helpful for prevention and treatment of ventilation induced lung injury.
- Conditions
- Acute Lung Injury
- Being tested
- mechanical ventilation
- Keywords
- dopamine,mechanical ventilation,lung injury
- Medical subject headings
- Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mechanical ventilationOther
mechanical ventilation protocol: tidal volume 6-8 ml/kg, positive end-expiratory pressure 5 cmH2O, oxygen concentration 40%; respiratory rate 10-15/min, inspiratory/expiratory ratio 1:1.5.
| Study group | Role | What they receive |
|---|---|---|
| ventilation | patients undergoing selective operation with general anesthesia(GA) and mechanical ventilation(MV) Receives: Other: mechanical ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation Coefficient (r) Between Duration of Mechanical Ventilation and DRD1 Expression
ImageJ software were used to get the Integrated Optical Density(IOD) of the chemiluminescent signal from the membranes of dopamine receptor 1(DRD1). The normalization was carried out by DRD1 IOD/total β-actin IOD for sample loading correction. In determination of the expression level of DRD1 in different time points, the investigators had a bulk preparation of normal placental protein which was set as a control. Analyze the correlation between duration of mechanical ventilation and DRD1 expression. If p value is less than 0.05, then its change is statically significant.
Measured: 20min-60min
Secondary outcomes (4)
Correlation Coefficient (r) Between Duration of Mechanical Ventilation and DRD2 Expression
ImageJ software were used to get the Integrated Optical Density(IOD) of the chemiluminescent signal from the membranes of dopamine receptor 2(DRD2). The normalization was carried out by DRD2 IOD/total β-actin IOD for sample loading correction. In determination of the expression level of DRD2 in different time points, the investigators had a bulk preparation of normal placental protein which was set as a control. Analyze the correlation between duration of mechanical ventilation and DRD2 expression. If p value is less than 0.05, then its change is statically significant.
Measured: 20min-60min
the Expression of TH in Lung Tissues
ImageJ software were used to get the Integrated Optical Density(IOD) of the chemiluminescent signal from the membranes of Tyrosine hydroxylase(TH). The normalization was carried out by TH IOD/total β-actin IOD for sample loading correction. In determination of the expression level of TH in different time points, the investigators had a bulk preparation of normal placental protein which was set as a control. Analyze the correlation between duration of mechanical ventilation and TH expression. If p value is less than 0.05, then its change is statically significant.
Measured: 20min-60min
the Expression of DDC in Lung Tissues
ImageJ software were used to get the Integrated Optical Density(IOD) of the chemiluminescent signal from the membranes of Dopa decarboxylase(DDC). The normalization was carried out by DDC IOD/total β-actin IOD for sample loading correction. In determination of the expression level of DDC in different time points, the investigators had a bulk preparation of normal placental protein which was set as a control. Analyze the correlation between duration of mechanical ventilation and DDC expression. If p value is less than 0.05, then its change is statically significant.
Measured: 20min-60min
the Expression of Ac-a-tubulin in Lung Tissues
ImageJ software were used to get the Integrated Optical Density(IOD) of the chemiluminescent signal from the membranes of acetylated-a-tubulin(Ac-a-tubulin). The normalization was carried out by Ac-a-tubulin IOD/total β-actin IOD for sample loading correction. In determination of the expression level of Ac-a-tubulin in different time points, the investigators had a bulk preparation of normal placental protein which was set as a control. Analyze the correlation between duration of mechanical ventilation and Ac-a-tubulin expression. If p value is less than 0.05, then its change is statically significant.
Measured: 20min-60min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2017
- Study start20 Mar 2017
- Primary completion22 Oct 2017
- Study completion1 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Lung InjuryStudies of the same condition, open and under way.
- More trials run by Xinhua Hospital, Shanghai Jiao Tong University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lai Jiang, chief doctor, Study chair, Xinhua Hospital affiliated to Medicine school,Shanghai Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03317431
- Sponsor's protocol ID
- XH-17-011
- Status last verified
- Mar 2017
- First submitted
- 17 Jul 2017
- Last updated
- 22 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- the Mechanism of the Downregulation of Dopamine Receptor in Mechanical Ventilation Induced Lung Injury
- ClinicalTrials.gov ID
- NCT03317431
- Acronym / sponsor ID
- XH-17-011
- Conditions
- Acute Lung Injury
- Keywords
- dopamine,mechanical ventilation,lung injury
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Xinhua Hospital, Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Study start
- 20 Mar 2017 (actual)
- Primary completion
- 22 Oct 2017 (actual)
- Study completion
- 1 Dec 2017 (actual)
- First posted
- 23 Oct 2017 (actual)
- Results
- Posted 22 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dopamine(DA) is a common neurotransmitter that has been known to regulate behavior, movement, cardiovascular，endocrine and gastrointestinal functions, but also functions as an important molecule engaging in the immune systems to possess anti-inflammatory effects. However, its role in ventilator-induced lung injury (VILI) is still unclear. Herein, this study aimed to investigate the therapeutic efficacy of dopamine on ventilation-induced lung endothelial barrier dysfunction and explore the possible underlying molecular mechanisms.
Detailed description
Mechanical ventilation is a critical intervention for patients with acute respiratory failure. However, lung overdistension induced by mechanical ventilation at high tidal volumes also causes pulmonary endothelial dysfunction. The injurious effect of mechanical stretch on pulmonary endothelium has been implicated in the development of ventilator-induced lung injury (VILI), which is characterized by pulmonary inflammation and particularly increased vascular permeability. In addition, the investigators and others have previously shown that mechanical stretch increases cultured lung endothelial monolayer permeability in vitro and promotes lung vascular permeability in mice Thus, elucidating the mechanisms underlying the mechanical stretch-induced lung endothelial barrier dysfunction may provide a novel clinical therapeutic target against VILI.
Dopamine is a neurotransmitter, which can also be produced outside the central nervous system. Lung alveolar epithelial cells represent an important source of extraneuronal dopamine, which has a significant role in local organ physiology. Dopamine D1 receptor (DRD1) and D2 receptor (DRD2) are present in lung tissues. Activation of D2DR induces NaKATPase gene expression. Moreover, activation of DRD1 results in the trafficking of NaKATPase to the basolateral membrane of type II alveolar epithelial cells, thus increasing lung liquid clearance during acute lung injury. Although the lung-protective effects of DA and its implication in the pathology of ALI are emerging, the mechanisms are still largely unknown.
In the present study, the investigators will analyze the influence of mechanical ventilation on dopamine receptors in the lung tissue of the participants, and explore whether DA could protect ventilation induced lung injury, which is helpful for prevention and treatment of ventilation induced lung injury.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ventilation | – | Other: mechanical ventilationpatients undergoing selective operation with general anesthesia(GA) and mechanical ventilation(MV) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- patients undergo elective lobectom
Key inclusion criteria (1 listed)
- Patients inclusion criteria: undergo elective lobectomy with general anesthesia and mechanical ventilation; classified as physical status I to III according to the American Society of Anesthesiologists Physical Status Classification System; Written informed consent is approved.
Key exclusion criteria (1 listed)
- Distant metastases: recent anaesthetics or mechanical ventilation treatment；children；women during pregnancy or lactation; being involved in other clinical subjects.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mechanical ventilationmechanical ventilation protocol: tidal volume 6-8 ml/kg, positive end-expiratory pressure 5 cmH2O, oxygen concentration 40%; respiratory rate 10-15/min, inspiratory/expiratory ratio 1:1.5. | Other | ventilation |
Primary outcome
Correlation Coefficient (r) Between Duration of Mechanical Ventilation and DRD1 Expression
Time frame: 20min-60min
ImageJ software were used to get the Integrated Optical Density(IOD) of the chemiluminescent signal from the membranes of dopamine receptor 1(DRD1). The normalization was carried out by DRD1 IOD/total β-actin IOD for sample loading correction. In determination of the expression level of DRD1 in different time points, the investigators had a bulk preparation of normal placental protein which was set as a control. Analyze the correlation between duration of mechanical ventilation and DRD1 expression. If p value is less than 0.05, then its change is statically significant.
4 secondary outcomes
Correlation Coefficient (r) Between Duration of Mechanical Ventilation and DRD2 Expression
Time frame: 20min-60min
the Expression of TH in Lung Tissues
Time frame: 20min-60min
the Expression of DDC in Lung Tissues
Time frame: 20min-60min
the Expression of Ac-a-tubulin in Lung Tissues
Time frame: 20min-60min
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lai Jiang, chief doctor study chair
Xinhua Hospital affiliated to Medicine school,Shanghai Jiaotong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Lung Injury, run by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation Coefficient (r) Between Duration of Mechanical Ventilation and DRD1 Expression (time frame: 20min-60min). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2018.